1. Field of the Invention
The invention concerns biosensors, i.e. sensing devices, in which biological molecules (e.g. enzymes) measure other substances which change the electrical properties of an electronic part (e.g. a semiconductor in a field effect transistor).
2. Relevant Technology and Literature
The concept of the biosensor has been known for a long time. A first application was the Malathion-(nerve-gas) sensor (Guilbaut, 1961). Immobilized cholinesterase was placed between two platinum-grids. The hydrolysis of the constantly added substrate (acetylcholin) is reduced in the presence of nerve-gas and thus an electronic signal created. Relevant literature includes: Sensors with the combination microbe-transistor (e.g. Karube Isao, Suzuki Shinchi "Biosensor for Fermentation and environmental control", Biotech 83, U.K. 83, pp. 625-632); Enzym-piezo-electrical crystal sensor (e.g. Cooper, Jeffrey B. et al., "Piezoelectric Sorption Anesthetic Sensor" in: IEEE Transactions on biomedical Engineering, USA 1981, Vol. BME-28 No. 6, pp. 459-466); Ionselective field effect transistor (e.g. McKinley, B.A. et al., "in vivo continuous monitoring of K+ in animals using ISFET probes", Med. Instruments (Baltimore), 14 (2) 1980)); Caras, S. and Janata Jiri, "field effect transistor sensitive to penicillin", Analytial Chem. USA 1980, 52, pp. 1935-1937; Schenk, John F. "FET for detection of biological reactions", U.S. Pat. No. 4,238,757; The combination of antibody and FET is also important J. Giaever, U.S. Pat. No. 3,853,469; Cox, U.S. Pat. No. 3,831,432; Umezawa Yoshi, Liposome immunoelectrode (Antibody signal enhanced via a complement-marker species), Proc. of the Int. Meeting on Chem. Sensors, Fukuoka, Japan, Sept. 19-22 1983); This collection is not complete, for further information consider e.g. Clermann, Robert J., "State of the art survey: Biochips" Technology 82 W00034; The MITRE Corp., USA 1982; and New Biosensor Devices, Biotech 83, U.K. 1983.
The signal from a biosensor should be as strong and as specific as possible. This led, after the first beginnings noted above, to the usage of macromolecules, e.g. enzymes or antibodies, and even bacteria, to get an electronic signal out of a biochemical (e.g. a sugar concentration) signal. These macromolecules have a high specific recognizing capability (antibody recognizes with high specificity its antigenic determinant). In practical applications, ions and foreign proteins interfere with the recognition of substances by these macromolecules. The great dimensions and complex structure of the macromolecules offer plenty opportunity for such an interference.
Besides this the dimension of the molecules used makes a direct implantation of the organic layer into the electronic layer impossible. An interfacing layer is used to get a connection between biological and electronic layer. The required wider separation between biological layer and electronic layer enhances the susceptibility to substantially interfering noise and increases the danger of losing the macromolecules not tightly enough bound at the organic layer (which is a limitation of the usage and life time under practical conditions).
A biosensor tries to convert a biological chemical signal (especially concentrations of biochemical substances) into an electronic signal (thus measuring it). To achieve this most efficiently a low signal to noise ratio is critical. This is an important practical problem for such devices. Further important practical problems are a long life and use-time and simple and low cost production of such biosensors. The invention shall help to ease these problems.